P940: AN OUTPATIENT MODEL FOR TECLISTAMAB STEP-UP DOSING ADMINISTRATION – INITIAL EXPERIENCES AT FOX CHASE CANCER CENTER BMT PROGRAM.
Authors: Asya Nina Varshavsky-Yanovsky, Michael Styler, Rashmi Khanal, Peter Abdelmessieh, Henry Fung
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Teclistamab, a bispecific T cell engager (BITE) targeting BCMA and CD3, was FDA approved in 10/2022 for treatment of RRMM after 4 prior lines of therapy, based on the results of phase 1-2 MajesTEC-1 study. Early toxicities of teclistamab include cytokine release syndrome (CRS) and immune effector cells associated neurotoxicity syndrome (ICANS). In the MajesTEC-1 study 70.9% patients had grade 1-2 CRS, only 0.6% had grade 3 CRS and none had grade 4; only 3% patients had ICANS, all grade 1-2. Median time to CRS onset was 2 days. To mitigate the risk of CRS/ICANS, teclistamab is administered in step-up dosing approach, with first 3 doses 0.06mg/kg, 0.3mg/kg, and 1.5mg/kg given 2-4 days apart, followed by 1.5mg/kg weekly. Due to concerns for CRS/ICANS, MajesTEC-1 protocol included 48h inpatient observation after each of the 3 step-up doses. Although inpatient observation is not mandated by FDA, it is recommended in the package insert. Inpatient observation imposes burden on the healthcare resources and affects patients' quality of life. Based on our experience in performing outpatient CAR-T therapy, we implemented outpatient teclistamab step-up dosing administration program. Here we report our initial experiences on the safety and feasibility of this approach. Aims: To evaluate safety and feasibility of the outpatient teclistamab administration model. Methods: We retrospectively reviewed toxicity outcomes of patients with RRMM who received outpatient teclistamab step-up dosing at Fox Chase Cancer Center in 12/2022-2/2023, after implementing institutional toxicity monitoring protocol. Eligible patients were required to stay within 1 hour from Fox Chase with a caregiver during the step-up observation period (day 1-10). Both the patient and caregiver received education on CRS & ICANS. Teclistamab step-up doses were administered on days 1, 3 and 8. Safety monitoring protocol included daily evaluation in the outpatient clinic as well as home monitoring of vital signs and scheduled 8pm physician phone call on days 1-5 and 8-10, within 48h observation window after 3 step-up doses. CBC, CMP, CRP and ferritin were monitored at each visit. Patients were observed for 6 hours in the clinic after each step-up dose administration. Patients with symptoms of CRS or ICANS of any grade were admitted to the inpatient unit for observation and management. All clinical staff have been trained in the diagnosis and management of CRS & ICANS. Results: Between 12/2022-2/2023, 9 patients completed outpatient teclistamab step-up dosing. Median age was 69y (46-79). All patients were triple-class exposed or refractory and 3 patients had prior BCMA CAR-T. No events of CRS or ICANS higher than grade 1 were observed. 5 patients (55.6%) did not have CRS or ICANS. 3 patients (33.3%) had one episode of grade 1 CRS each. Of the 3 CRS events, two occurred within 24h of day 1 dose, and one was associated with concurrent grade 1 ICANS. Both patients were treated with 1 dose of tocilizumab, and the patient with ICANS also received dexamethasone, with prompt resolution of symptoms. No recurrent CRS/ ICANS was observed with second and third step-up doses. Additional patient had grade 1 CRS within 24h after day 3 dose and was observed inpatient, but did not require treatment. Summary/Conclusion: Our outpatient teclistamab administration model with close toxicity monitoring and prompt hospitalization for toxicity management is safe and feasible in heavily pre-treated RRMM patients and allows significant reduction of inpatient stay, resulting in significant healthcare savings and improvement of patients' experience. Keywords: Bispecific, Cytokine release syndrome, Real world data, Myeloma